Treg-Cell-Derived IL-35-Coated Extracellular Vesicles Promote Infectious Tolerance
Jeremy A. Sullivan, Yusuke Tomita, Ewa Jankowska−Gan, Diego Lema, Matt Arvedson, Ashita Nair, William Bracamonte‐Baran, Ying Zhou, Kristy Meyer, Weixiong Zhong, Deepali V. Sawant, Andrea L. Szymczak-Workman, Qianxia Zhang, Creg J. Workman, Seungpyo Hong, Dario A.A. Vignali, William J. Burlingham
Abstract
(iTr35) T cells. Furthermore, IL-35 producers, although rare, secrete Ebi3 and p35 on extracellular vesicles (EVs) targeting a 25- to 100-fold higher number of T and B lymphocytes, causing them to acquire surface IL-35. This surface IL-35 is absent when EV production is inhibited or if Ebi3 is genetically deleted in Treg cells. The unique ability of EVs to coat bystander lymphocytes with IL-35, promoting exhaustion in, and secondary suppression by, non-Treg cells identifies a novel mechanism of infectious tolerance.